Antibiotic Resistance by Enzymatic Modification of Antibiotic Targets

Antibiotic resistance remains a significant threat to modern medicine. Modification of the antibiotic target is a resistance strategy that is increasingly prevalent among pathogens. Examples include resistance to glycopeptide and polymyxin antibiotics that occurs via chemical modification of their molecular targets in the cell envelope. Similarly, many ribosome-targeting antibiotics are impaired by methylation of the rRNA. In these cases, the antibiotic target is subjected to enzymatic modification rather than genetic mutation, and in many instances the resistance enzymes are readily mobilized among pathogens. Understanding the enzymes responsible for these modifications is crucial to combat resistance. Here, we review our current understanding of enzymatic modification of antibiotic targets as well as discuss efforts to combat these resistance mechanisms.